Glucose transport into the rat tibial nerve from blood, across blood vessels of the nerve endoneurium, is by a factilitated transport system that demonstrates stereospecificity and saturation, and allows matching of transport and nerve metabolic demand. Permeabilities of the blood-nerve barrier to ions and nonelectrolytes are low, indicating limited exchange between blood and nerve. However, the barrier does not regulate nerve calcium, which slowly equilibrates between nerve and blood during chronic hypocalcemia and hypercalcemia. Capillaries of the nerve vasculature become more permeant during experimental diabetes, resulting in a peripheral neuropathy in rats accompanied by nerve edema. Blood flow in the rat sciatic nerve, as measured with laser doppler flowmetry, does not seem to be autoregulated during acute hypotension. Histoflourescence methods indicate adrenergic innervations of blood vessels on the surface of the nerve, but not neuronal innervation within the nerve endoneurium. Vesicular profiles are demonstrated in the perineurium of frog nerve and in endothelial cells of pial blood vessels, using rapid freezing and freeze substitution methods, demonstrating that vesicles do not contribute to transcellular macromolecular transport. Alkaline phosphatase within vesicles indicate that they are microdomains for enzymatic activity. Wallerian degeneration alters the permeability of the blood nerve barrier tissues of the frog for up to 6 weeks.